[New markers of cardio-renal links in chronic kidney disease]

L Iu Milovanova, Iu S Milovanov, L V Kozlovskaia, N A Mukhin
Terapevticheskiĭ Arkhiv 2013, 85 (6): 17-24

AIM: To study the clinical significance of determining the serum concentration of phosphorus and calcium metabolism regulators--the morphogenetic proteins FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD).

SUBJECTS AND METHODS: The serum levels of FGF-23 (a human FGF-23 ELISA kit with full-length anti-FCF-23 monoclonal antibodies) and Klotho (a human alpha-K1 ELISA with anti-Klotno antibodies) were investigated in 70 patients with Stages I--VD CKD (41 patients with chronic glomerulonephritis, including 10 with nephritis in systemic diseases, 22 with tubulointerstitial nephritis, and 7 with hypertensive nephroslerosis). The morphogenetic proteins were studied by the specialists of the LiTECH diagnostic laboratory according to the standard protocol.

RESULTS: As CKD progressed from Stage I to VD, there were increased FGF-23 concentrations and decreased Klotho levels in the examinees' serum. The highest FGF-23 level and low Klotho concentration were noted in the group of patients on regular hemodialysis treatment (Stage VD). There was a strong inverse correlation between Klotho levels and proteinuria, C-reactive protein, and protein-energy insufficiency, which suggests that these factors influence the serum level of Klotho. The serum levels of FGF-23 and intact parathyroid hormone correlated with these values to a lesser degree. Analysis of the content of the morphogenetic proteins in patients with anemia versus those with CKD of the same stages and target hemoglobin values revealed low Klotho concentrations and high FGF-23 levels (r = 0.602; p < 0.01 and r = -0.450; p < 0.01, respectively). Forty-nine hypertensive patients showed a direct strong relationship between elevated serum FGF-23 levels and an inverse strong one between the reduced serum Klotho levels and the increased posterior left ventricular wall (r = 0.552; p < 0.01 and r = -0,587; p < 0.01, respectively). The same strong association was found between the higher serum level of FCF-23 (r = 0.492; p < 0.01) and the concentration of Klotho (r = -0.537; p < 0.01) and peripheral vascular resistance index (as evidenced by Doppler ultrasound study).

CONCLUSION: Along with the active participation of the morphogenetic proteins (FGF-23 and Klotho) in mineral metabolism and its disturbances in CKD, their role is apparent in the development of cardiovascular events (in particular, through the involvement in the processes of vascular calcification and cardiac remodeling), anemia (through the possible effect on iron metabolism, enhanced ischemia of renal interstitial tissue with impaired Klotho production), and protein-energy insufficiency (through the participation in the processes of inflammation, oxidative stress, and protein synthesis).

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